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TitleStructural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity.
Journal, issue, pagesSci Adv, Vol. 9, Issue 23, Page eadg0330, Year 2023
Publish dateJun 9, 2023
AuthorsJames A Williams / Marco Biancucci / Laura Lessen / Sai Tian / Ankita Balsaraf / Lynn Chen / Chelsy Chesterman / Giulietta Maruggi / Sarah Vandepaer / Ying Huang / Corey P Mallett / Ann-Muriel Steff / Matthew James Bottomley / Enrico Malito / Newton Wahome / Wayne D Harshbarger /
PubMed AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels of S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated in silico and 15 were produced for biochemical analysis. S2D14, which contains 20 computationally designed mutations within the S2 domain and a rationally engineered D614G mutation in the SD2 domain, has an ~11-fold increase in protein yield and retains RBD antigenicity. Cryo-electron microscopy structures reveal a mixture of populations in various RBD conformational states. Vaccination of mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than adjuvanted S-2P against the SARS-CoV-2 Wuhan strain and four variants of concern. S2D14 may be a useful scaffold or tool for the design of future coronavirus vaccines, and the approaches used for the design of S2D14 may be broadly applicable to streamline vaccine discovery.
External linksSci Adv / PubMed:37285422 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.3 Å
Structure data

28531

8epn

EMDB-28531, PDB-8epn:
Cryo-EM structure of SARS-CoV-2 Spike trimer S2D14 in the 3-RBD Down conformation
Method: EM (single particle) / Resolution: 2.8 Å

28532

8epp

EMDB-28532, PDB-8epp:
Cryo-EM structure of SARS-CoV-2 Spike trimer S2D14 with two RBDs in the open conformation
Method: EM (single particle) / Resolution: 3.1 Å

28533

8epq

EMDB-28533, PDB-8epq:
Cryo-EM structure of SARS-CoV-2 Spike trimer S2D14 with two RBDs exposed
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / Glycoprotein / trimer

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